%0 Journal Article
%A Leroux,
%A Roué,
%A Gouyon,
%A Biran,
%A Zheng,
%A Zhao,
%A Jacqz-Aigrain,
%T O-2 Population and developmental pharmacokinetic analysis to evaluate and optimise cefotaxime dosing regimen in neonates and young infants
%D 2017
%R 10.1136/archdischild-2017-esdppp.2
%J Archives of Disease in Childhood
%P A1-A1
%V 102
%N 10
%X Background Cefotaxime is one of the most frequently prescribed antibiotics for the treatment of Gram-negative bacterial sepsis in neonates. However, the dosing regi-mens routinely used in clinical practice vary considerably. The objective of the present study was to conduct a population pharmacokinetic study of cefotaxime in neonates and young infants in order to evaluate and optimise the dosing regimen.Methods An opportunistic sampling strategy com-bined with population pharmacokinetic analysis using NONMEM software was performed. Cefotaxime concentrations were measured by high-performance liquid chromatography tandem mass spectrometry. Developmental pharmacokinetics-pharmacodynamics, the microbiological pathogens, and safety aspects were taken into account to optimise the dose.Results The pharmacokinetic data from 100 neonates (gestational age [GA] range, 23 to 42 weeks) were modeled with an allometric two compartment model with first-order elimination. The median values for clearance and volume of distribution at steady state were 0.12 litre/h/kg of body weight and 0.64 litre/kg, respectively. The covariate analysis showed that current weight, GA, and postnatal age [PNA] had significant impacts on ce-fotaxime pharmacokinetics. Monte Carlo simulations demonstrated that the current dose recommendations underdosed the older newborns. A model-based dosing regimen of 50 mg/kg twice a day to four times a day, according to GA and PNA, was established. The associated risk of overdose for the proposed dosing regimen was 0.01%.Conclusion We determined the population pharma cokinetics of cefotaxime and established a model based dosing regimen to optimise treatment for neonates and young infants.
%U https://adc.bmj.com/content/archdischild/102/10/A1.2.full.pdf